OBJECTIVE: To compare the registration accuracy of cone beam computed tomography (CBCT) images while registering to virtual craniodentofacial patients based on soft tissue and the dentition registration method. METHODS: Virtual dentofacial patients out of 13 selected participants who needed CBCT scanning were established by impression with a registered-block impression (RBI) based on digital dental images, three-dimensional (3D) facial images and maxillofacial CBCT images. CBCT images were processed in the Mimics software program, establishing the craniofacial virtual patients based on CBCT images (CCTs). Registration between virtual patients from RBI and CCT, using the soft tissue in lower half face (STE) and dentition (DTN) as the reference area, respectively, forming two kinds of virtual craniofacial patients based on digital dental images, 3D facial images and skeletal images of CBCT (hiding the soft tissue and dental casts from CBCT). Three-dimensional deviation analysis was performed in the upper half face and lower half face of facial images from CBCT between two kinds of virtual craniodentofacial patients and compared with 3D facial images from RBI and recorded as root mean square error (RMSE). Paired-t test was used to compare the deviations of RMSEs between the upper and lower half of the face and the upper half of the face of facial images from CCT, respectively, between the two kinds of virtual craniodentofacial patients based on STE and DTN methods. RESULTS: Paired-t tests showed that there was no statistically significant difference between the upper and lower half faces of facial images from CCT between STE and DTN (P>0.05), but the deviation of RMSEs of the upper half face of facial images from CCT in STE was smaller than those in DTN [(1.696±0.420) mm vs. (1.752±0.424) mm, P < 0.01]. CONCLUSION The registration accuracy of CBCT registered in virtual craniodentofacial patients using soft tissue as the reference area was higher.
Humans ; Cone-Beam Computed Tomography/methods* ; Imaging, Three-Dimensional/methods* ; Male ; Face/anatomy & histology* ; Female ; Adult ; Image Processing, Computer-Assisted/methods* ; Young Adult ; User-Computer Interface

OBJECTIVE: To elucidate the role and underlying mechanism of ubiquitin-specific protease 35 (USP35) in ferroptosis of rheumatoid arthritis-fibroblast like synoviocytes (RA-FLS), thereby enhancing our comprehension of the pathogenesis of RA and identifying potential therapeutic targets for its treatment. METHODS: (1) RA-FLS were cultured in vitro and transduced with lentiviral vectors to establish stable cell lines: A USP35-knockdown line (short hairpin ribonucleic acid of USP35, shUSP35) and its control (negtive control of short hairpin ribonucleic acid, shNC), as well as a overexpression of USP35 line (USP35 OE) and its control (Vector). To investigate the role of USP35 in ferroptosis regulation, a ferroptosis model was induced in RA-FLS by treatment with 1 μmol/L Erastin. The cells were divided into six groups: shNC, shNC + Erastin, shUSP35 + Erastin, Vector, Vector + Erastin, and USP35 OE + Erastin. (2) Cell viability was detected using the cell counting kit-8 (CCK-8). (3) Reactive oxygen species (ROS), malondialdehyde (MDA), glutathione/glutathione disulfide (GSH/GSSG) ratios, and Ferrous ion (Fe²⁺) levels were measured using specific assay kits to evaluate oxidative stress, lipid peroxidation, and glutathione redox status in the cells. (4) Protein expression levels of solute carrier family 7 member 11 (SLC7A11) and glutathione peroxidase 4 (GPX4) were detected using Western blotting to investigate their potential involvement in USP35-mediated ferroptosis regulation. RESULTS: (1) Compared with the shNC +Erastin group, the cell viability of the shUSP35+Erastin group was significantly decreased (P < 0.001), while it was notably increased in the USP35 OE+Erastin group compared with the Vector+Erastin group (P < 0.001). These findings indicated that USP35 could alleviate the inhibitory effect of Erastin on RA-FLS cell viability. (2) In comparison to the shNC+Erastin group, the levels of ROS (P < 0.001), MDA (P < 0.05), and Fe²⁺ (P < 0.001) were significantly elevated, and the GSH/GSSG ratio was increased (P < 0.05) in the shUSP35+Erastin group. Conversely, the levels of ROS (P < 0.001), MDA (P < 0.05), and Fe²⁺ (P < 0.05) were significantly decreased, and the GSH/GSSG ratio was decreased (P < 0.05) in the USP35 OE+Erastin group compared with the Vector+Erastin group. These results suggested that USP35 could inhibit Erastin-induced oxidative stress and lipid peroxidation in RA-FLS. (3) In Erastin-induced RA-FLS, the expression of USP35 was positively correlated with the protein levels of SLC7A11 and GPX4, indicating a potential mechanism by which USP35 regulated ferroptosis in these cells. CONCLUSION USP35 inhibits ferroptosis in RA-FLS, potentially through the increased expression of SLC7A11 and GPX4.
Ferroptosis ; Humans ; Arthritis, Rheumatoid/metabolism* ; Synoviocytes/pathology* ; Reactive Oxygen Species/metabolism* ; Ubiquitin-Specific Proteases/metabolism* ; Fibroblasts/pathology* ; Cell Survival ; Piperazines/pharmacology* ; Endopeptidases/metabolism* ; Cells, Cultured ; Cell Line ; Amino Acid Transport System y+

OBJECTIVE: To investigate the hepatotoxicity of alkaloids from Euodiae Fructus combined with berberine (BBR) in Zuojin Pill, and to preliminarily explore the possible detoxification mechanism of the combination components. METHODS: The combination ratio of components was determined by the maximum concentration (Cmax) of the chemical components in Zuojin Pill. HepG2 cell model was used to investigate the combined toxicity of the hepatotoxic components from Euodiae Fructus, such as evodiamine (EVO) or dehydroevodiamine (DHED), with BBR for 48 h. The experimental groups were set as follows: the vehicle control group, the EVO group, the DHED group, the BBR group, and the combination group of EVO or DHED with BBR. The cell counting kit-8 (CCK-8) method was used to determine the cell viability, and the combination index (CI) was used to determine the combined toxicity of the components. The alanine transaminase (ALT), aspartate aminotransferase (AST), lactate dehydroge-nase (LDH), and alkaline phosphatase (ALP) activities as well as total bilirubin (TBIL) content in the cell culture supernatant were detected. The protein expression levels of bile acid transporters, such as bile salt export pump (BSEP) and multidrug resistance-associated protein 2 (MRP2), were detected by Western blot. The intracellular malondialdehyde (MDA) content and superoxide dismutase (SOD) activity in HepG2 cells were detected. RESULTS: Compared with EVO or DHED group, the combination of EVO 1 μmol/L with BBR 10 μmol/L or DHED 50 μmol/L with BBR 35 μmol/L significantly increased cell viability of HepG2 cells (P < 0.01), with CI values of 77.89 or 4.49, respectively, much greater than 1. Significant decreases in the activities of ALT, AST, LDH, ALP, and TBIL content in the cell culture supernatant were found in both combination groups (P < 0.05, P < 0.01). Compared with the EVO group, the combination of EVO with BBR upregulated the protein expression levels of BSEP and MRP2. Compared with the DHED group, the combination of DHED with BBR significantly downregulated the protein expression levels of BSEP and MRP2 (P < 0.01). Compared with EVO or DHED group, the combination of EVO or DHED with BBR significantly reduced the MDA content in HepG2 cells (P < 0.05, P < 0.01). CONCLUSION A certain ratio of BBR combined with EVO or DHED had an antagonistic effect on HepG2 cytotoxicity, which might be related to regulating the expression of bile acid transpor-ters, and reducing lipid peroxidation damage.
Humans ; Hep G2 Cells ; Berberine/pharmacology* ; Drugs, Chinese Herbal/toxicity* ; Evodia/chemistry* ; Alkaloids/pharmacology* ; Cell Survival/drug effects* ; Multidrug Resistance-Associated Proteins/metabolism* ; Multidrug Resistance-Associated Protein 2 ; Quinazolines

OBJECTIVE: To investigate the changes and symmetry of facial soft tissue during posed smile, to analyze the feature of posed smile in different gender, and verify the reproducibility of posed smile. METHODS: Three-dimensional (3D) facial images of 41 adults (16 males and 25 females with an average age of 26.76±2.70 years) which were taken by FaceScan three-dimensional sensor, including one rest position and two posed smile images. Then these images were imported into 3D soft tissue analysis software for model repositioning. 3D morphable model method (3DMM) was carried out to automatic landmarks setting. After that, the measurement of the eyes, cheeks, nose and perioral area were carried out for 3D soft tissue analysis. Finally, the changes and symmetry of the soft tissues between the two expression states and the gender differences during the posed smiles were compared. Meanwhile, the reproducibility of posed smile was statistically tested. RESULTS: Compared with the rest position, except for nasolabial angle (1.45°±7.65°), the measurements of 3D soft tissue in other region were changed in posed smile (P < 0.001). It should be noted that the eye region was also significantly changed (P < 0.001). Furthermore, the prominent feature of posed smile was that the alar base length became longer, the upper and lower vermilions were narrow and thin, and the mentolabial furrows became shallow. Meanwhile the chin extended anteriorly while the mouth retracted; During posed smile, the labial fissure asymmetry [2.78 (1.73, 3.49) mm], mid-infraorbital asymmetry [2.36 (1.22, 3.27) mm] and outercanthal asymmetry [2.31(1.29, 2.80) mm] were most apparent. Compared with the rest position, the asymmetry was not significantly increased except for cheilion and alar curvature points during the posed smile (P>0.05). In the posed smile, the changes of the right palpebral fissure height and the thickness of lower vermilion (|Li-Stoi| _z) of males were greater than those of females (P < 0.05), and asymmetry of exocanthion and cheekbone increased more than that of females (P < 0.05). There was no obvious difference between the two posed smiles. CONCLUSION In this study, during the posed smile the soft tissues of the eyes, cheeks, nose, lips and chin changed in different degrees, and the asymmetry of cheilion and alar curvature point was greater than that of the rest position; In addition, the reproducibility of posed smile was excellent, which can be a reference for clinical aesthetics and functional research of smile.
Humans ; Smiling/physiology* ; Female ; Male ; Adult ; Imaging, Three-Dimensional/methods* ; Face/anatomy & histology* ; Young Adult ; Facial Expression

OBJECTIVE: To utilize Spinal Cord Toolbox (SCT) to measure the morphological parameters of healthy cervical spinal cords and explore the impact of gender, age and vertebral levels on them. METHODS: A retrospective study was conducted, collecting cervical spinal cord magnetic resonance images of 184 healthy adults. Then, cross-sectional area (CSA), eccentricity, antero-posterior diameter (AP) and right-left diameter (RL) were each computed for every subject. Then, impacts of gender, age and vertebral level on CSA and eccentricity were explored. Moreover, linear correlation analysis was conducted among CSA, AP and RL. RESULTS: The CSA of the cervical spinal cord in males was significantly larger than that in females at C2~C7 segments (P＜0.05) . For C2~C6 segments, there was no statistically significant difference in CSA between the young and middle-aged groups, but both were significantly larger than that of the elderly group. CSA of C4 was the largest whereas CSA of C7 was the smallest. Eccentricity values of C4 and C5 were significantly larger than those of other vertebral levels (P＜0.05). Linear correlation was established between CSA, AP and RL at C2~C7 segments. CONCLUSION The results allow for minimizing inter-subject variability using normalization, and thereby highlighting the importance of morphological parameters as biomarkers in the research of cervical spinal lesions.
Humans ; Female ; Male ; Retrospective Studies ; Middle Aged ; Adult ; Cervical Cord/anatomy & histology* ; Magnetic Resonance Imaging ; Young Adult ; Aged ; Cervical Vertebrae/anatomy & histology*

OBJECTIVE: To investigate the biological effect of medical recombinant human-derived collagen functional dressings in wound healing. METHODS: MTT assay and RTCA assay were used to detect cell toxicity and proliferation. Scratch assay and Transwell cell migration assay were used to detect cell motility and migration ability. Enzyme-linked immunosorbent assay was used to detect the contents of vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF), and platelet-endothelial cell adhesion molecule (CD31) in the supernatant of four types of cells. After animal surgery, the surgical wound was taken at 1 week, 4 weeks and 13 weeks, respectively, for hematoxylin eosin (HE) staining and immunohistochemistry to observe the inflammatory response and CD31 expression of the wound. RESULTS: Medical recombinant human-derived collagen functional dressing promotes cell proliferation and migration, enhances wound angiogenesis by upregulating the expression of VEGF, FGF, and CD31 in human dermal vascular endothelial cells (HDVEC) and human vascular endothelial cells (HVEC), thereby improving local blood supply to the wound, regulating the inflammatory response of the wound, and accelerating wound healing. CONCLUSION Recombinant type Ⅲ humanized collagen plays an important role in wound healing.
Humans ; Wound Healing/drug effects* ; Recombinant Proteins/pharmacology* ; Animals ; Cell Proliferation ; Cell Movement ; Collagen/pharmacology* ; Vascular Endothelial Growth Factor A/metabolism* ; Bandages ; Platelet Endothelial Cell Adhesion Molecule-1/metabolism* ; Endothelial Cells ; Fibroblast Growth Factors/metabolism*

OBJECTIVE: To evaluate the efficacy and safety of a hospital-made resuscitation pack, a Chinese medicinal herbal compound formula designed to enhance recovery in post-bronchoscopy patients. METHODS: In this randomized, single-blind, placebo-controlled clinical trial, eligible patients were randomly assigned 1:1 to either the treatment or control groups. The patients in the treatment group applied the resuscitation pack, which contained aromatic compounded Chinese herbs. The patients in the control group applied a hospital-made, single herb placebo pack. Packs were placed on the Tiantu (CV 22) acupuncture point for 4 h as soon as the bronchoscopy finished. Efficacy indicators, such as recovery time, patients' symptoms including nausea and dizziness, and adverse events (AEs) were observed and compared. The outcome indices were evaluated at baseline, 1 and 24 h after the bronchoscopy. Subgroup analysis was further performed by patients' age and depth of sedation. RESULTS: When applying generalized estimating equations (GEE) to evaluate the intensity of post-bronchoscopy nausea and vomiting, the intensity was lower in the treatment group (163 cases) compared with the control group (162 cases; 95% CI: 0.004, 0.099, P=0.03]. Also, significantly lower intensity of nausea was observed in the 60-70 years of age subgroup (95% CI: 0.029, 0.169, P=0.006) and deep sedation subgroup (95% CI: 0.002, 0.124; P=0.04). There was no significant difference in dizziness between two groups by GEE (95% CI: -0.134, 0.297; P=0.459). In addition, no serious AEs were observed in either group. CONCLUSIONS Our study found that the resuscitation pack markedly improved patients' symptoms by reducing nausea and vomiting after bronchoscopy without AEs, compared with placebo in the perioperative period. (Trial registration No. ChiCTR2000038299).
Humans ; Male ; Middle Aged ; Female ; Bronchoscopy/adverse effects* ; Single-Blind Method ; Aged ; Drugs, Chinese Herbal/adverse effects* ; Treatment Outcome ; Resuscitation ; Adult ; Medicine, Chinese Traditional

OBJECTIVE: To study hesperetin-induced vasorelaxation after depolarizing contraction in human umbilical veins (HUVs) to elucidate the role of L-type Ca²⁺ channel (LTCC) and related signaling pathway. METHODS: Isometric tension recording was performed in HUV rings pre-contracted with K⁺. Hesperetin relaxing mechanism was investigated using a LTCC opener (BayK8644) and blockers of cyclic nucleotides and phosphodiesterases (PDEs). Whole-cell patch-clamping in A7r5 cells, a rat vascular smooth muscle cell line, was performed to study the effect of hesperetin on LTCC current. RESULTS: After depolarizing precontraction, hesperetin induced HUV relaxation concentration-dependently and endothelium-independently; 1 mmol/L hesperetin reduced denuded HUV ring tension by 68.7% ± 4.3% compared to matching vehicle, osmolality, and time controls (P<0.0001). Importantly, hesperetin competitively inhibited BayK8644-induced contraction, shifting the half maximal effective concentration of BayK8644 response from 1.08 nmol/L [95% confidence interval (CI) 0.49-2.40] in vehicle control to 11.30 nmol/L (95% CI 5.45-23.41) in hesperetin (P=0.0001). Moreover, hesperetin elicited further vasorelaxation in denuded HUV rings pretreated with inhibitors of soluble guanylyl cyclase, adenylyl cyclase, PDE3, PDE4, and PDE5 (P<0.01), while rings pretreated with PDE1 inhibitors could not be relaxed by hesperetin (P>0.05). However, simultaneously applying inhibitors of soluble guanylyl cyclase and adenylyl cyclase could not inhibit hesperetin's effect (P>0.05). In whole-cell patch-clamping, hesperetin rapidly decreased LTCC current in A7r5 cells to 66.7% ± 5.8% (P=0.0104). CONCLUSIONS Hesperetin diminishes depolarizing contraction of human vascular smooth muscle through inhibition of LTCC, and not cyclic nucleotides nor PDEs. Our evidence supports direct LTCC interaction and provides additional basis for the use of hesperetin and its precursor hesperidin as vasodilators and may lead to future vasodilator drug development as a treatment alternative for cardiovascular diseases.
Hesperidin/pharmacology* ; Humans ; Calcium Channels, L-Type/metabolism* ; Umbilical Veins/physiology* ; Muscle Contraction/drug effects* ; Animals ; Rats ; Calcium Channel Blockers/pharmacology* ; Vasodilation/drug effects* ; Muscle Relaxation/drug effects*

OBJECTIVE: To investigate the therapeutic efficacy of cinnamaldehyde (CA) on systemic Candida albicans infection in mice and to provide supportive data for the development of novel antifungal drugs. METHODS: Ninety BALB/c mice were randomly divided into 3 groups according to a random number table: CA treatment group, fluconazole (positive control) group, and Tween saline (negative control) group, with 30 mice in each group. Initially, all groups of mice received consecutive intraperitoneal injections of cyclophosphamide at 200 mg/kg for 2 days, followed by intraperitoneal injection of 0.25 mL C. albicans fungal suspension (concentration of 1.0 × 10⁷ CFU/mL) on the 4th day, to establish an immunosuppressed systemic Candida albicans infection animal model. Subsequently, the mice were orally administered CA, fluconazole and Tween saline, at 240, 240 mg/kg and 0.25 mL/kg respectively for 14 days. After a 48-h discontinuation of treatment, the liver, small intestine, and kidney tissues of mice were collected for fungal direct microscopic examination, culture, and histopathological examination. Additionally, renal tissues from each group of mice were collected for (1,3)- β -D-glucan detection. The survival status of mice in all groups was monitored for 14 days of drug administration. RESULTS: The CA group exhibited a fungal clearance rate of C. albicans above 86.7% (26/30), significantly higher than the fluconazole group (60.0%, 18/30, P<0.01) and the Tween saline group (30.0%, 9/30, P<0.01). Furthermore, histopathological examination in the CA group revealed the disappearance of inflammatory cells and near-normal restoration of tissue structure. The (1,3)-β-D-glucan detection value in the CA group (860.55 ± 126.73 pg/mL) was significantly lower than that in the fluconazole group (1985.13 ± 203.56 pg/mL, P<0.01) and the Tween saline group (5910.20 ± 320.56 pg/mL, P<0.01). The mouse survival rate reached 90.0% (27/30), higher than the fluconazole group (60.0%, 18/30) and the Tween saline group (30.0%, 9/30), with a significant difference between the two groups (both P<0.01). CONCLUSIONS CA treatment exhibited significant therapeutic efficacy in mice with systemic C. albicans infection. Therefore, CA holds potential as a novel antifungal agent for targeted treatment of C. albicans infection.
Animals ; Acrolein/pharmacology* ; Candida albicans/physiology* ; Mice, Inbred BALB C ; Candidiasis/pathology* ; Antifungal Agents/therapeutic use* ; Mice ; Fluconazole/therapeutic use* ; Kidney/drug effects* ; Female

Tubulointerstitial fibrosis (TIF) is one of the key indicators in evaluating the renal function of patients. Mild TIF can cause a vicious cycle of renal tubular glomerular injury and aggravate renal disease. Therefore, studying the mechanisms underlying TIF is essential to identify therapeutic targets, thereby protecting the renal function of patients with timely intervention. Astragaloside IV (AS-IV) is a Chinese medicine component that has been shown to inhibit the occurrence and progression of TIF via multiple pathways. Previous studies have reported that AS-IV protected against TIF by inhibiting inflammation, autophagy, endoplasmic reticulum stress, macrophages, and transforming growth factor-β1, which laid the foundation for the development of a new preventive and therapeutic option for TIF.
Saponins/pharmacology* ; Triterpenes/pharmacology* ; Humans ; Fibrosis ; Animals ; Kidney Tubules/drug effects* ; Kidney Diseases/pathology*